E2F regulation of Phosphoglycerate kinase (Pgk) gene is functionally important in Drosophila development

Our study focuses on understanding the changes in chromatin accessibility in the Pgk-DeltaE2F mutant that takes place during flight muscles development in Drosophila. E2F binding sites were mutated upstream Pgk gene. E2F/Dp/Rbf were no longer recruited to this regulatory region. As a result of this, the expression of Pgk mRNA was downregulated, which led to reduced levels in many metabolites that are glycolytic and TCA intermediates. Using ATAC-seq we determined that there was a global reduction in chromatin accessibility in the mutant compared to control, and it was accompagnied by a widespread reduction in gene expression, including metabolic genes. In addition we identified a broad range of phenotypes when analyzing the functional relevance of E2F regulation on Pgk gene. These phenotypes range from low ATP content, abnormal mitochondrial morphology, shortened life span to embrionic lethality. Furthermore, defects in high-energy consuming organs, such as ovaries and muscles, were found. In sum, our results illustrate the pleiotropic effects on metabolism, gene expression and development in the Pgk-deltaE2F animals, which underlies the importance of E2F regulation on a single E2F target, Pgk. Overall design: ATAC-Seq on nuclei extracted from thoracic muscles enriched for flight muscles staged at pharate (96h APF). The Pgk.deltaE2F mutant was compared to control. A total of 2 replicates per genotype were processed.